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POEMS syndrome is a rare paraneoplastic syndrome related to an underlying plasma cell disorder (PCD) that is monoclonal λ-restricted in >95% of cases [16][742][1156]. The term POEMS is an acronym encompassing the features Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal PCD, and Skin changes. However, not all of these features are required to make a diagnosis, and there are other additional important clinical features not covered by the acronym (such as elevated vascular endothelial growth factor [VEGF] levels, sclerotic bone lesions, extravascular volume overload and Castleman disease) [743]. Whilst the pathogenesis of the condition is poorly understood, increased levels of cytokines (including VEGF) are thought to play a major role [1156].

Although SPE and sFLC analysis constitute a simple and efficient diagnostic screen for the majority of monoclonal gammopathies (Chapter 23), the diagnostic sensitivity of this algorithm is inadequate for POEMS syndrome, where the monoclonal protein production is often small (median 1.1 g/L) [1156]. A large screening study by Katzmann et al. concluded that serum immunofixation electrophoresis (sIFE) should be performed in addition to SPE and sFLC analysis when a diagnosis of POEMS syndrome is suspected [134], whereas the European Myeloma Network recommend sIFE, uIFE and FLC testing to evaluate patients with suspected POEMS syndrome [1188].

Wang et al. [742] studied the utility of HLC analysis in a large group of 90 patients with POEMS syndrome (58 IgA, 30 IgG and 2 light chain only). An abnormal IgA HLC ratio was present in 79% (46/58) IgA patients and also one of the light chain only patients. In comparison, an abnormal IgG HLC ratio was present in 63% (19/30) IgG patients. When all patients were considered, the incidence of HLC pair suppression increased along with the monoclonal protein concentration, from 14% in patients without a quantifiable monoclonal protein, to 44% in subjects with a monoclonal protein >5 g/L (p=0.039). An abnormal HLC ratio predicted clinical relapse, when measured either at baseline or after treatment, and the significance increased when more extreme ratios were considered (both p<0.001).

Altinier et al. [885] compared involved HLC and VEGF concentrations during follow-up for 7 POEMS patients: HLC showed a reasonable agreement with VEGF throughout the monitoring period. This was in contrast to the involved FLC values, which showed a poor correlation with VEGF.

In summary, initial data suggest that HLC assays identify disease clonality in the majority of POEMS patients, and HLC analysis may have prognostic value.

Answers

No, because the monoclonal heavy chain lacks the HLC epitopes. However, subtracting HLC measurements from total immunoglobulin concentrations will give an estimate of the monoclonal heavy chain (Section 34.3).

Polyclonal elevations of sFLCs are present in most patients with POEMS syndrome but less than 20% have abnormal sFLC ratios (Section 34.4).